Astrocytes Kill Neurons In ALS

Astrocytes carrying a mutated version of a protein that causes amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig's disease) are responsible for the death of motor neurons, report two papers in the May 2007 issue of Nature Neuroscience. These findings suggest that stem cell therapy focused on replacing damaged neurons may not be feasible in ALS, because diseased astrocytes would be expected to damage the replacement neurons.

Mutations in the gene for superoxide dismutase (SOD1) cause some cases of ALS, in which progressive degeneration of motor neurons leads to paralysis and eventually death. In both studies, the authors expressed this mutant protein in single cell types in culture. Motor neurons degenerated and died when cocultured with astrocytes expressing mutant SOD1, while mutant SOD1 in neurons, fibroblasts or microglia did not cause neuronal death.

Przedborski and colleagues additionally report that the astrocytes expressing mutant SOD1 killed only the neurons that degenerate in ALS, not other types of neurons, and that this was due to a soluble toxic factor released by the astrocytes. If this toxic factor can be identified in future studies, this finding may offer novel strategies for therapy.